Corticosteroid Benefits Without Side Effects

Researchers work toward pill to replace corticosteroids like Prednisone.

By Mary Anne Dunkin

Imagine a medication with all the anti-inflammatory power of a corticosteroid but without corticosteroid’s detrimental effects on the bone or other side effects. Thanks in part to work by Arthritis Foundation-supported researchers, such a drug – using a protein called glucocorticoid-induced leucine zipper (GILZ) – may one day be available.

In a study reported in the April 15, 2008 issue of the Journal of Cellular Biochemistry, Xingming Shi, PhD, and his colleagues at the Medical College of Georgia in Augusta found that the GILZ protein mimics the action of corticosteroids and blocks signals from inflammatory cytokines such as tumor necrosis factor-alpha (TNF-a) and interleukin-1 (IL-1), known to play a role in the inflammation and destruction of rheumatoid arthritis and other inflammatory diseases.

The advantage of the GILZ protein over corticosteroid medications is that it could potentially prevent the bone loss that is often a side-effect of long-term steroid treatment and also might not create the stores of excess fat common in people who take those medications, says Shi, whose research focuses on the cellular and molecular mechanisms of corticosteroid-induced osteoporosis and the search for new treatments of the problem.

The reason is that both bone and fat are derived from mesynchymal stem cells.

Traditional corticosteroids shift the balance between bone and fat production and cause more fat cells to accumulate. Excess fat leads to more cytokines ­– chemicals that signal for inflammation, which stimulate production of bone-destroying cells called osteoclasts and inhibit bone-forming cells called ostetoblasts. Permanently expressing GILZ, however, prevents mesynchymal cells from differentiating into fat cells and instead increases bone formation.

Shi already has developed a cell line that continuously expresses GILZ. Eventually, he would like to develop a GILZ pill that could be taken in place of a traditional corticosteroid.

Imagine a medication with all the anti-inflammatory power of a corticosteroid but without corticosteroid’s detrimental effects on the bone or other side effects. Thanks in part to work by Arthritis Foundation-supported researchers, such a drug – using a protein called glucocorticoid-induced leucine zipper (GILZ) – may one day be available.

In a study reported in the April 15, 2008 issue of the Journal of Cellular Biochemistry, Xingming Shi, PhD, and his colleagues at the Medical College of Georgia in Augusta found that the GILZ protein mimics the action of corticosteroids and blocks signals from inflammatory cytokines such as tumor necrosis factor-alpha (TNF-a) and interleukin-1 (IL-1), known to play a role in the inflammation and destruction of rheumatoid arthritis and other inflammatory diseases.

The advantage of the GILZ protein over corticosteroid medications is that it could potentially prevent the bone loss that is often a side-effect of long-term steroid treatment and also might not create the stores of excess fat common in people who take those medications, says Shi, whose research focuses on the cellular and molecular mechanisms of corticosteroid-induced osteoporosis and the search for new treatments of the problem.

The reason is that both bone and fat are derived from mesynchymal stem cells.

Traditional corticosteroids shift the balance between bone and fat production and cause more fat cells to accumulate. Excess fat leads to more cytokines ­– chemicals that signal for inflammation, which stimulate production of bone-destroying cells called osteoclasts and inhibit bone-forming cells called ostetoblasts. Permanently expressing GILZ, however, prevents mesynchymal cells from differentiating into fat cells and instead increases bone formation.

Shi already has developed a cell line that continuously expresses GILZ. Eventually, he would like to develop a GILZ pill that could be taken in place of a traditional corticosteroid.